The Chemist’s Role In Academic Drug Discovery

As major pharmaceutical companies continue to move away from research and discovery, it is often stated that academia will play an increasingly important role in future drug discovery efforts. With the academic model for drug discovery as it stands today, let’s hope not.

The evidence that led me to this conclusion is quite striking. Some time ago I sat through a fascinating presentation by a virology group searching for a specific type of antiviral drug. The presenters explained that they had screened a library of several thousand compounds against their chosen target, and this screen yielded a single confirmed lead structure. Sounds promising so far, but wait.

After some exciting in vivo results, the authors began to write up their results for publication in a peer-reviewed journal. At this point, they learned that the exact structure they identified through screening was already a known lead structure for their chosen target. It’s unclear whether this compound was included in the library because of its known antiviral activity. In any case, much effort was expended to obtain a known result.

What’s troubling is not that library screening is fast, powerful, and occasionally redundant. Rather it is that this is where this chapter of the researchers’ drug discovery story ended. Since when did drug discovery end at lead structure identification? As perhaps one of the few chemists in a roomful of biologists and clinician scientists, all I could think was that this is where the story should begin, not end, as anyone familiar with pharmaceutical chemistry knows.

This anecdote would be unremarkable if it were unique, but all too often in academia the drug discovery process ends the same way. Although the value of small-molecule library screening or testing of known safe drugs for off-target effects is undeniable, too often these tools appear to be used as a means to remove chemists from the iterative process of drug discovery. This is not a successful recipe for development of innovative and effective therapeutics.

We chemists should be asking why chemists are frequently omitted from academic research proposals that seek drug discovery and grapple with solutions. Perhaps only when federal granting institutions increase emphasis on the importance of a collaborating chemist on drug discovery proposals will this futile and unproductive system really change.